Deregulation of idiotype expression. Induction of tolerance in an anti-idiotypic response.

Author:

Ortiz-Ortiz L,Weigle W O,Parks D E

Abstract

The induction of tolerance in an anti-idiotypic response was attempted by in vivo exposure to excess idiotype. Monoclonal immunoglobulin from the anti-p-azobenzenearsonate (ABA) hybridoma R16.7 was used as a representative of cross-reactive idiotype-positive (CRI+) antibodies because this hybridoma protein (HP) shares one or more closely related public idiotypic determinants with the serum CRI in A/J mice. Immunologic unresponsiveness was established by a single injection of the R16.7 idiotype and persisted for at least 6 wk. The level of circulating anti-idiotypic antibodies in tolerized A/J mice was significantly depressed after immunogenic challenge with eigher antigen, ABA-keyhole limpet hemocyanin (KLH), or the idiotype R16.7 HP. Experimental depletion of anti-idiotypic antibodies by tolerization allowed assessment of immunoregulation within this altered idiotype-anti-idiotype network. Deregulation of idiotype expression in tolerized mice challenged with ABA-KLH was manifest with up to 96% of the anti-ABA antibodies cross-reacting with the R16.7 idiotype. This selective enhancement of a major idiotype was accomplished without substantial alteration of the level of the overall anti-hapten response. Both the unresponsiveness established in anti-idiotypic antibody-producing cells and the enhanced synthesis in idiotype-producing cells were stable upon adoptive transfer into lethally irradiated, syngeneic recipients. Finally, previous immunization with the antigen ABA-KLH interfered with the induction of unresponsiveness to the idiotype. This interference is presumed to be mediated by prior activation of anti-idiotypic cells and/or antibody because injection of antigen with tolerogenic idiotype did not abrogate tolerance induction.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

Cited by 9 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Immunoalienation;Annals of the New York Academy of Sciences;2006-01-25

2. Tolerance: Facts and views — 1983;Survey of Immunologic Research;1984-06

3. Mechanisms of Idiotypic Control of the Antibody Repertoire;The Biology of Idiotypes;1984

4. Idiotypic Determinants Used in the Analysis of Antibody Diversification and as Regulatory Targets;Annals of the New York Academy of Sciences;1983-12

5. Tolerance for self IG at the level of the Ly1+ T cell.;Journal of Experimental Medicine;1983-12-01

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